An important role of α-hemolysin in extracellular vesicles on the development of atopic dermatitis induced by Staphylococcus aureus.

Skin barrier disruption and dermal inflammation are key phenotypes of atopic dermatitis (AD). Staphylococcus aureus secretes extracellular vesicles (EVs), which are involved in AD pathogenesis. Here, we evaluated the role of EVs-associated α-hemolysin derived from S. aureus in AD pathogenesis. α-hem...

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Autores principales:	Sung-Wook Hong, Eun-Byul Choi, Taek-Ki Min, Ji-Hyun Kim, Min-Hye Kim, Seong Gyu Jeon, Byung-Jae Lee, Yong Song Gho, Young-Koo Jee, Bok-Yang Pyun, Yoon-Keun Kim
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6d35659879274668ab94424b16bcfc52
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spelling	oai:doaj.org-article:6d35659879274668ab94424b16bcfc522021-11-25T06:09:38ZAn important role of α-hemolysin in extracellular vesicles on the development of atopic dermatitis induced by Staphylococcus aureus.1932-620310.1371/journal.pone.0100499https://doaj.org/article/6d35659879274668ab94424b16bcfc522014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24992681/?tool=EBIhttps://doaj.org/toc/1932-6203Skin barrier disruption and dermal inflammation are key phenotypes of atopic dermatitis (AD). Staphylococcus aureus secretes extracellular vesicles (EVs), which are involved in AD pathogenesis. Here, we evaluated the role of EVs-associated α-hemolysin derived from S. aureus in AD pathogenesis. α-hemolysin production from S. aureus was detected using western blot analyses. The cytotoxic activity of α-hemolysin on HaCaT keratinocytes was evaluated by measuring cell viability after treating cells with soluble and EVs-associated α-hemolysin. To determine the type of cell death, HaCaT keratinocytes were stained with annexin V and 7-AAD. The in vivo effects of α-hemolysin were evaluated by application of soluble and EV-associated α-hemolysin on the mouse skin. The present study showed that increased α-hemolysin was produced by S. aureus colonized on AD patients compared to healthy subjects. α-hemolysin production was also related to AD severity. In addition, EV-associated α-hemolysin was more cytotoxic to HaCaT keratinocytes than soluble α-hemolysin, and α-hemolysin-negative EVs did not induce keratinocyte death. EV-associated α-hemolysin induced necrosis, but soluble α-hemolysin induced apoptosis of keratinocytes. In vivo, skin barrier disruption and epidermal hyperplasia were induced by soluble and EV-associated α-hemolysin. However, AD-like dermal inflammation was only caused by EV-associated α-hemolysin. Moreover, neither skin barrier disruption nor AD-like skin inflammation was induced by α-hemolysin-negative EVs. Taken together, α-Hemolysin secreted from S. aureus, particularly the EV-associated form, induces both skin barrier disruption and AD-like skin inflammation, suggesting that EV-associated α-hemolysin is a novel diagnostic and therapeutic target for the control of AD.Sung-Wook HongEun-Byul ChoiTaek-Ki MinJi-Hyun KimMin-Hye KimSeong Gyu JeonByung-Jae LeeYong Song GhoYoung-Koo JeeBok-Yang PyunYoon-Keun KimPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 7, p e100499 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sung-Wook Hong Eun-Byul Choi Taek-Ki Min Ji-Hyun Kim Min-Hye Kim Seong Gyu Jeon Byung-Jae Lee Yong Song Gho Young-Koo Jee Bok-Yang Pyun Yoon-Keun Kim An important role of α-hemolysin in extracellular vesicles on the development of atopic dermatitis induced by Staphylococcus aureus.
description	Skin barrier disruption and dermal inflammation are key phenotypes of atopic dermatitis (AD). Staphylococcus aureus secretes extracellular vesicles (EVs), which are involved in AD pathogenesis. Here, we evaluated the role of EVs-associated α-hemolysin derived from S. aureus in AD pathogenesis. α-hemolysin production from S. aureus was detected using western blot analyses. The cytotoxic activity of α-hemolysin on HaCaT keratinocytes was evaluated by measuring cell viability after treating cells with soluble and EVs-associated α-hemolysin. To determine the type of cell death, HaCaT keratinocytes were stained with annexin V and 7-AAD. The in vivo effects of α-hemolysin were evaluated by application of soluble and EV-associated α-hemolysin on the mouse skin. The present study showed that increased α-hemolysin was produced by S. aureus colonized on AD patients compared to healthy subjects. α-hemolysin production was also related to AD severity. In addition, EV-associated α-hemolysin was more cytotoxic to HaCaT keratinocytes than soluble α-hemolysin, and α-hemolysin-negative EVs did not induce keratinocyte death. EV-associated α-hemolysin induced necrosis, but soluble α-hemolysin induced apoptosis of keratinocytes. In vivo, skin barrier disruption and epidermal hyperplasia were induced by soluble and EV-associated α-hemolysin. However, AD-like dermal inflammation was only caused by EV-associated α-hemolysin. Moreover, neither skin barrier disruption nor AD-like skin inflammation was induced by α-hemolysin-negative EVs. Taken together, α-Hemolysin secreted from S. aureus, particularly the EV-associated form, induces both skin barrier disruption and AD-like skin inflammation, suggesting that EV-associated α-hemolysin is a novel diagnostic and therapeutic target for the control of AD.
format	article
author	Sung-Wook Hong Eun-Byul Choi Taek-Ki Min Ji-Hyun Kim Min-Hye Kim Seong Gyu Jeon Byung-Jae Lee Yong Song Gho Young-Koo Jee Bok-Yang Pyun Yoon-Keun Kim
author_facet	Sung-Wook Hong Eun-Byul Choi Taek-Ki Min Ji-Hyun Kim Min-Hye Kim Seong Gyu Jeon Byung-Jae Lee Yong Song Gho Young-Koo Jee Bok-Yang Pyun Yoon-Keun Kim
author_sort	Sung-Wook Hong
title	An important role of α-hemolysin in extracellular vesicles on the development of atopic dermatitis induced by Staphylococcus aureus.
title_short	An important role of α-hemolysin in extracellular vesicles on the development of atopic dermatitis induced by Staphylococcus aureus.
title_full	An important role of α-hemolysin in extracellular vesicles on the development of atopic dermatitis induced by Staphylococcus aureus.
title_fullStr	An important role of α-hemolysin in extracellular vesicles on the development of atopic dermatitis induced by Staphylococcus aureus.
title_full_unstemmed	An important role of α-hemolysin in extracellular vesicles on the development of atopic dermatitis induced by Staphylococcus aureus.
title_sort	important role of α-hemolysin in extracellular vesicles on the development of atopic dermatitis induced by staphylococcus aureus.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/6d35659879274668ab94424b16bcfc52
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An important role of α-hemolysin in extracellular vesicles on the development of atopic dermatitis induced by Staphylococcus aureus.

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